The science supporting the efficacy of magnesium for major depression and other psychiatric disorders, testing for magnesium deficiency, and which forms and dosages are most effective.

Depression, a life-threatening psychiatric disorder, lies at the confluence of biochemical, hormonal, immunological, and neurodegenerative variables, which intersect to generate the pro-inflammatory state with which depression is associated. A major public health issue, depression is estimated to become one of the top three contributors to the global burden of diseases within a few years. Not only does depression consume a sizable portion of health care expenditures, but it is considered to be an independent risk factor for metabolic, cardiovascular, and neuropsychiatric disorders (1).

Current treatments are predicated upon a misguided serotonin theory of depression, and are accompanied by a laundry list of deleterious side effects ranging from sexual dysfunction to homicidality (2, 3, 4). Antidepressant medications likewise significantly increase the risk of all-cause mortality, or death from any cause, as well as heart disease, leading researchers to deem this class of pharmaceuticals as harmful to the general population (5). This, in combination with data indicating that antidepressants are clinically equivalent to placebo, render them an unfavorable option (6), especially considering that they offer little in the way of resolving the root cause.

Magnesium: The Miracle Mineral

Rather than resorting to psychotropic drugs, it would be prudent to explore whether magnesium (Mg) supplementation improves depression, since this essential mineral is implicated in the pathophysiology of this disorder. Magnesium may be indeed branded as miraculous given its essentiality as a cofactor to over three hundred enzymatic reactions (7). It is second only to potassium in terms of the predominant intracellular cations, or ions residing in cells that harbor a positive charge (7).

 Magnesium is fundamentally involved in protein production, synthesis of nucleic acids, cell growth and division, and maintenance of the delicate electrolyte composition of our cells (7). It also imparts stability to the membranes of the energy factories of our cells called mitochondria (7). As articulated by researchers, “The physiological consequences of these biochemical activities include Mg’s central roles in the control of neuronal activity, cardiac excitability, neuromuscular transmission, muscular contraction, vasomotor tone, and blood pressure” (7).

The biological effects of magnesium are widespread. When deficient, magnesium is correlated with systemic inflammation. Not only does magnesium sufficiency promote cardiovascular health, relaxing the smooth muscles that comprise blood vessels and preventing high levels of vascular resistance that cause hypertension, but it also plays a role in musculoskeletal health and prevents sarcopenia, osteoporosis, and fractures (8). Magnesium is essential to regulation of sleep (9) and vitamin D metabolism (10) as well as neural plasticity and cognitive function.

However, food processing and industrial agriculture, including monoculture crop practices and the use of magnesium-devoid fertilizers, have led to soil erosion and depletion of magnesium content in our food (7). Magnesium is likewise removed from most drinking water supplies, rendering magnesium deficiency an inevitability (11). As such, our daily intake of magnesium has steadily declined from 500 milligrams (mg) per day to 175 mg per day (7). The nutrient-poor, energy-dense dietary patterns which have come to dominate the industrialized landscape are also insufficient in the fiber-rich fruits and vegetables which contain magnesium.

Animal Studies Propose a Role for Magnesium in Depression

Preliminary animal studies pointed to a role of magnesium in depression, as depletion of magnesium in the diet of mice lead to enhanced depression- and anxiety-related behavior such as increased immobility time in the forced swim test (12). In the forced swim test, a common assay for examining depression-like behavior in rodents, the animal is confined to a container filled with water and observed as it attempts to escape. The time in which the animal exhibits immobility is used as a barometer of despair, indicating that the animal has succumbed to a fate of drowning (1).

This model is confirmed by studies showing that administering substances with antidepressant properties such as Hypericum perforatum, also known as St. John’s Wort, can significantly decrease the time the animal spends without locomotor activity (12). In addition, the time the animal spends immobilized is influenced by many of the factors that are changed as a consequence of depression in humans, such as drug-withdrawal-induced anhedonia, impaired sleep, and altered food consumption (1).

Human Studies Confirm the Role of Magnesium in Depression

There is a paucity of research on the influence of specific micronutrients in depression and results are inconsistent, but several studies have revealed low serum magnesium in this mood disorder. It is well-documented, for example, that dietary magnesium deficiency in conjunction with stress can lead to neuropathologies and symptoms of psychiatric disorders. Researchers echo this sentiment, stating that, “Dietary deficiencies of magnesium, coupled with excess calcium and stress may cause many cases of other related symptoms including agitation, anxiety, irritability, confusion, asthenia, sleeplessness, headache, delirium, hallucinations and hyperexcitability” (11, p. 362).

The Hordaland Health study in Western Norway illustrated an inverse association between standardized energy-adjusted magnesium intake and depression scores, meaning that people who consumed less magnesium had higher rates of depression (13). When the serum and cerebrospinal fluid of acutely depressed patients diagnosed with major depressive disorder or bipolar patients in a depressive episode were compared to healthy controls, the calcium to magnesium ratio was found to be elevated in the former (14). Calcium and magnesium are minerals which antagonize one another and compete for absorption, since each of these minerals is a divalent cation (a positive ion with a valence of two). Suicidality, one of the primary manifestations of severe depression, is accompanied by low cerebrospinal fluid levels of magnesium despite normal calcium levels, lending credence to the role of magnesium in positive emotionality (15).

Magnesium Effective in Bipolar Disorder, Fibromyalgia, PMS, and Chronic Fatigue Syndrome

A formulation of magnesium aspartate hydrochloride known as Magnesiocard has been shown to invoke mood-stabilizing effects in patients with severe rapid cycling bipolar disorder in one open study label (16). In half of the patients treated, this magnesium preparation had results equivalent to lithium, the standard of care for this patient population, such that the researchers suggested: “The possibility that Magnesiocard could replace or improve the efficacy of lithium as a preventive treatment of manic-depressive illness merits further clinical investigation” (16, p. 171). When used as an adjunctive therapy in severe, therapy-resistant mania, magnesium sulphate infusions significantly reduced the use of lithium, benzodiazepines and neuroleptics, so much so that the researchers concluded that it “may be a useful supplementary therapy for the clinical management of severe manic agitation” (17, p. 239).

In another randomized trial of elderly patients with type 2 diabetes and magnesium deficiency, elemental magnesium administered at 450 mg per day was found to have equivalent efficacy to 50 mg of the antidepressant drug Imipramine in treating depressive symptoms (18). Magnesium citrate taken at 300 mg per day has likewise been shown to decrease depression and other symptoms in patients with fibromyalgia as indicated by significant decreases in the fibromyalgia impact questionnaire (FIQ) and Beck depression scores (19).

Data also indicate that supplementation with 360 mg of magnesium administered to women with premenstrual syndrome (PMS) three times a day in the second half of the cycle is effective for so-called negative affect and other premenstrual-related mood symptoms (20). Lastly, intramuscular magnesium sulphate administered every week for six weeks has been proven to be effective in improving emotional state and other parameters in chronic fatigue syndrome (CFS) (21).

Mechanism of Action for Antidepressant Effects of Magnesium

According to researchers, “Biological systems discussed to be involved in the pathophysiology of affective disorders and the action of mood stabilizing drugs are affected by Mg, such as the activity of the hypothalamus–pituitary–adrenocortical (HPA) system, corticotropin releasing factor (CRF)-, GABA- and glutamatergic (via NMDA receptors) neurotransmission and several transduction pathways including protein kinase C” (12). Not only that, but magnesium elicits similar effects on nocturnal hormonal secretion and sleep brain waves to lithium salts, which are used as a treatment modality for bipolar disorder, supporting the role of magnesium as a mood stabilizer (22).

Magnesium operates as an agonist, or a stimulatory molecule, for γ-aminobutyric acid (GABA) receptors (22). GABA is the main inhibitory neurotransmitter in the central nervous system. By binding to the GABA receptor and replicating the effects of GABA, magnesium may alleviate anxiety. Magnesium may also elicit its antidepressant effects by acting as an inorganic antagonist of N-methyl-d-aspartic acid (NMDA) receptor function (Poleszak et al., 2007). Receptor antagonists are ligands, or substances, which bind to a receptor but inhibit its activity rather than activating it. NMDA receptors, which occur on the surface of nerve cells, are activated in part by glutamate, one of the excitatory amino acids in the brain.

Researchers state that, “Dysfunction of NMDA receptors seems to play a crucial role in the neurobiology of disorders such as Parkinson’s diseaseAlzheimer’s diseaseepilepsy, ischemic stroke, anxiety and depression,” such that, “ligands interacting with different sites of NMDA receptor complex are widely investigated as potential agents for the treatment of a variety of neuropsychiatric disorders” (22). In fact, drug inhibitors at the NMDA receptor complex, such as ketamine, demonstrate antidepressant effects (23, 24), but also induce such severe side effects that their clinical utility is limited (31). Magnesium, on the other hand, may have a similar mechanism of action by interfering with NMDA receptor activation without the adverse consequences of drug-induced NMDA receptor blockade (25).

Recent Study Proves Efficacy of Oral Magnesium for Depression

A recent open-label, randomized, cross-over trial was conducted in outpatient primary care clinics on 126 adults diagnosed with depression (26). During the intervention, 248 mg of elemental magnesium chloride per day, obtained from four 500 mg tablets, was administered for six weeks and compared to six weeks of no treatment, and subjects were evaluated for changes in depressive symptoms (26).

Magnesium administration results in clinically significant improvements in scores on both the Patient Health Questionnaire-9 (PHQ-9), a validated measure of the severity of depression and response to treatment, as well as the Generalized Anxiety Disorders-7 (GAD-7), a sensitive self-reported screening tool for severity of anxiety disorders (26). Impressively, results appeared in as little as two weeks, representing the dramatic improvement that nutrient restoration can facilitate (26). Impressively, however, magnesium exerted anti-depressant effects regardless of baseline magnesium level. It also exhibited efficacy independent of the gender, age, or baseline severity of depression of subjects, as well as their use of antidepressant medications (26). The authors of the study conclude, “Magnesium is effective for mild-to-moderate depression in adults. It works quickly and is well tolerated without the need for close monitoring for toxicity” (26).

Populations At Risk for Magnesium Deficiency

Half of the population of the United States was found to consume less than the recommended amount of magnesium when estimated a decade ago (27). Not only is magnesium lost with certain medical conditions, but this mineral is excreted as a consequence of biological activities such as sweating, urinating, and defecating as well as excess production of stress hormones (7, 11). In addition, because low magnesium has been correlated with various disease states, increasing magnesium status may mitigate risk of these diseases.

For instance, researchers note that, “Low magnesium intakes and blood levels have been associated with type 2 diabetes, metabolic syndrome, elevated C-reactive protein, hypertension, atherosclerotic vascular disease, sudden cardiac death, osteoporosis, migraine headache, asthma, and colon cancer” (27, p. 153). In addition, magnesium deficiency at a cellular level “elicits calcium-activated inflammatory cascades independent of injury or pathogens” (27, p. 153). Low magnesium is associated with systemic inflammation, and inflammation is at the root of most chronic and degenerative diseases.

Testing for Magnesium and Food Sources of Magnesium

While the first inclination of some physicians may be to test magnesium levels for an objective parameter of deficiency, the widely used serum or plasma magnesium does not accurately reflect magnesium levels stored in other tissues (28, 29). In addition, both this hematological index of magnesium status, referred to as total magnesium, and the erythrocyte magnesium level, indicative of the levels of magnesium inside red blood cells, are not negatively affected until severe magnesium deprivation has occurred (7). Therefore, these testing methodologies are not accurate enough to catch preliminary or subclinical magnesium deficiency.

Good food sources of magnesium include pumpkin and squash seed kernels, Brazil nuts, almonds, cashews, peanuts, pine nuts, quinoa, spinach, Swiss chard, beet greens, potatoes, artichoke hearts, dates, bananas, coconut milk, prickly pear, black beans, lima beans, soybeans, and seafood sources including halibut, abalone, anchovy, caviar, conch, crab, oyster, scallop, snail, and pollock. However, it is important to note that magnesium can be leeched from vegetables when food is boiled, and that fiber in excess can decrease magnesium absorption by increasing gastrointestinal motility (7).

Most Bioavailable Forms of Magnesium

As elucidated by the researchers, “Over-the-counter magnesium can be offered as an alternative therapy to those patients hesitant to begin antidepressant treatment and is easily accessible without a prescription” (26). Because the soil is no longer enriched in magnesium, supplementation may be warranted. Organic salts of magnesium, including the acetate, ascorbate, aspartate, bicitrate, gluconate, and lactate forms are more soluble and biologically active over the magnesium mineral salts such as magnesium oxide, magnesium carbonate, magnesium chloride, and magnesium sulfate (7).

However, case studies have shown remarkably rapid recovery from major depression, in less than seven days, when magnesium glycinate and magnesium taurinate are administered at dosages of 125 to 300 mg with each meal and at bedtime (11). Magnesium threonate may also be explored as a therapeutic option, as it may have better penetrance of the blood brain barrier and restore neurological levels of magnesium. This form, which is delivered directly to the brain, may improve cerebral signaling pathways and synaptic connections between nerve cells as well as support learning and memory, although the studies have been conducted in animal models (30).

Researchers report that magnesium is usually effective for treating depression in general use, and that comorbid conditions occurring in these case studies, including “traumatic brain injury, headache, suicidal ideation, anxiety, irritability, insomnia, postpartum depression, cocaine, alcohol and tobacco abuse, hypersensitivity to calcium, short-term memory loss and IQ loss were also benefited” by magnesium supplementation (11, p. 362). Barring abnormal kidney function, the Institute of Medicine sets the upper tolerable limit for intake at 350 mg of elemental magnesium per day, but there are few adverse side effects documented unless consumed in inordinate doses (26).

Before changing your medication or nutraceutical regimen, always consult a functional or integrative medical doctor for contraindications. However, given the benign nature of magnesium supplementation and the ubiquity of magnesium insufficiency, depressedpatients should be offered this as a first line strategy alongside a holistic root-cause resolution approach to treating depression

Spinach Helps Protect Eyes from Macular Degeneration

Spinach Helps Protect Eyes from Macular Degeneration

Most of us will have macular degeneration as we age. But we can slow this process and even prevent it with certain dietary strategies. Learn how spinach and other foods and supplements can prevent the leading cause of blindness.

The macula in the center of the retina of our eyes can easily become damaged when it is unprotected. The macula can be damaged by looking into the sun or with prolonged bright light exposure. But the risk of this type of damage – or age-related macular degeneration – is decreased when the macula is protected by its own macular pigment.

When this macular pigment becomes thinner, it lets in a type of light that easily damages the macula. One of the most damaging is called blue light. Blue light is the prevalent emission among computers and many TVs. It is also a component of the sun – though the sun also has many healthy wavelengths of light that balance its blue light.

Yes, healthy macula maintains a yellow pigment that shields blue light. This might be compared to the macula having its own pair of sunglasses. This macular pigment is made up of three yellowcarotenoids – specifically lutein, zeaxanthin and meso-zeaxanthin.

Towards the middle of the macula, zeaxanthin is more concentrated, reaching 75 percent. Away from the middle, the dominant component is lutein, with 65 percent or more of the total. Among all tissues, the macula contains the highest concentration of these carotenoids.

When our consumption of these important carotenoids runs low, the macular pigment shield of the macula thins. This can progressively happen with age, but it can also run low among those with low levels of these nutrients – lutein and zeaxanthin – in the diet.

Low macular pigment optical density

When our macular pigment becomes thinner, this is called low macular pigment optical density or low MPOD. Low MPOD has been linked with macular degeneration in a number of studies. This can occur with age – age-related macular degeneration – or exposure – exposure-related macular degeneration.

In both instances, as the macular pigment thins, blue light gets in and damages the macula. This is because the carotenoid pigment absorbs blue light.

Blue light is part of the visible spectrum that comes from the sun, but it is one of the longer wavelengths, at between 400 and 500 nanometers. Meanwhile, ultraviolet radiation ranges from 220 to 400 nanometers, with UV-C the shortest at 220-280 nm and UV-A at 320-400 nm. Ultraviolet radiation under 295 nanometers is typically filtered out by the cornea. But longer UV wavelengths and blue light gets through the cornea along with the rest of the visible spectrum (400 to 700 nanometers).

As mentioned, blue light is also disproportionately emitted with computers, phones and other digital displays. This is one reason why the eyes tend to get more tired after looking at these screens – depending upon the levels of our macular pigment density.

How do I know if my macular pigment density is low?

Each of us will have a unique thickness of macular pigment, depending on our age, general health and diet. But our levels could be significantly low. This increases our risk of macular degeneration – or greater degeneration as our bodies age.

Most blindness is produced from macular degeneration.

The thickness or density of our macular pigment can be measured by an instrument such as the QuantifEye made by ZeaVision. This test is not invasive and can be done in the optometrist’s office. The macular pigment optical density will be scored between 0 to 1. An MPOD score of less than .21 is considered low. A score of .22 to .44 is considered medium range, and scores between .45 to 1.0 are considered high – and healthier. The greater the pigment density, the more the macula is protected against radiation damage.

A thicker macular pigment density also can significantly improve our vision. It can help prevent photosensitivity for example. Thicker pigment can also help us view natural environments and see at night.

It is not as if our macula pigment density is fixed, however. Our diet can significantly change the pigment.

So you think this is far-fetched?

Spinach consumption increases macular pigment

Japanese researchers tested the notion that ones dietary habits could significantly change our macular pigment density. So they recruited 11 healthy people and tested 22 eyes. They were non-smokers, aged between 21 and 45 years old.

The researchers gave the subjects testing for the health of their macula and their macular pigment densities. They also gave them blood tests and general eye exams.

Then they had the subjects eat 75 grams of frozen spinach each day for two months.

The 75 grams of frozen spinach was tested and contained 10 mg of lutein – the sister carotenoid with zeaxanthin. They also gave the subjects food frequency questionnaires to measure the rest of their diets.

The researchers found that the eyesight of the subjects was improved – measured as visual acuity. They also found their macular pigment densities were significantly increased. These improvements were seen at both one month and two months after the spinach regimen began. They confirmed the relationship between the lutein by seeing increased blood levels of lutein among the subjects.

The researchers concluded:

“Constant intake of lutein-rich spinach increased both MPOD and serum lutein concentrations.”

Other studies confirm macula/carotenoid link

Many other studies have shown that lutein, zeaxanthin and/or meso-zeaxanthin carotenoids increase macular health:

A study from Germany’s Friedrich Schiller University gave 20 patients with macular degeneration either 50 milliliters of a kale extract or a placebo for four weeks. They also studied the patients for two weeks prior and four weeks after (washout period) the supplementation.

The daily dose of the kale extract contained 10 milligrams of lutein and 3 milligrams of zeaxanthin.

The researchers found that their macular pigment densities increased significantly among the treatment group. But during the washout period, their densities and blood levels of these carotenoids decreased significantly. They were better than at the beginning, but they did drop off when the kale extract was stopped.

This of course indicates that we have to consistently eat these carotenoid-rich foods.

A number of studies have confirmed this. In research published in the British Journal of Nutrition, scientists conducted a meta-analysis of multiple studies. These studies investigated the relationship between dietary consumption of foods with lutein and zeaxanthin and their macular health.

The research compared those who consumed the lowest levels of these plant carotenoids with those who consumed the highest levels. The researchers found that age-related macular degeneration was reduced by 26 percent for those who consumed the most of these carotenoid-rich foods.

What about carotenoid supplementation?

In terms of supplementation, a 2015 study from Ireland’s University of Ulster and the University of Wisconsin tested 67 people with early age-related macular degeneration. They divided them into three groups and given different supplement formulations. For three years, one group took a supplement with 20 mg of lutein and .86 mg of zeaxanthin per day. Another group received 10 mg per day of meso-zeaxanthin, 2 mg of zeaxanthin and 10 mg of lutein each day. The third group received 10 mg per day of meso-zeaxanthin, 2 mg of zeaxanthin and 10 mg of lutein each day. After three years, the patients were all tested for macular degeneration and macular pigment density. This was compared to their levels at the beginning of the study.

The research found that the macular pigments of all the supplemented patients improved similarly. However, those who took the supplements with the meso-zeaxanthin had moderately better results in both the macular pigment density and their contrast sensitivity.

The researchers also found that the macular pigments of the patients continued to increase between the second and third year of supplementation among those where the supplements included meso-zeaxanthin.

The researchers also noted that none of the patients taking the supplements progressed to advanced age-related macular degeneration.

Sources of lutein and zeaxanthin

Yes, spinach certainly contains some of the highest levels of these carotenoids. This is why the researchers focused upon spinach consumption. According to the USDA’s nutritional database, a cup of raw spinach contains as much as 13.3 milligrams of lutein. Spinach also contains as much as 5.9 milligrams of zeaxanthin and up to 12.6 milligrams of lutein and zeaxanthin combined.

Other good dietary sources of lutein and zeaxanthin including spinach are (in milligrams (mg)):

• Kale – up to 26.5 mg lutein/zeaxanthin and 2.2 mg zeaxanthin
• Spinach – up to 12.6 mg lutein/zeaxanthin, 13.3 lutein and 5.9 mg zeaxanthin
• Collard greens – up to 15.3 mg lutein/zeaxanthin and 5.1 mg zeaxanthin
• Turnip greens – up to 12.1 mg lutein/zeaxanthin, 0.4 mg zeaxanthin
• Broccoli – up to 3.5 mg lutein/zeaxanthin and 1.6 mg lutein
• Green peas – up to 2.3 mg lutein/zeaxanthin, 2.2 mg lutein
• Yellow corn – up to 3 mg lutein/zeaxanthin, 0.6 mg lutein and 0.9 mg zeaxanthin

Other good sources of zeaxanthin/lutein combined include oranges, tangerines, lettuce, beans, celery, peaches and carrots – again in order of content.

Confused about lutein, zeaxanthin and meso-zeaxanthin?

The reality is that lutein, zeaxanthin and meso-zeaxanthin have the same chemical formulas. The main difference is in their double bonds among their rings.

As a result, they have similar effects, and they are also often combined within foods. Some foods supply distinct lutein and others supply distinct zeaxanthin. But most foods that contain either contain them in combination. This means that the human body will derive all from eating these – yet distinctly more of either will be absorbed when they are isolated.

The two main compounds – lutein and zeaxanthin – are strictly produced by plants. The third carotenoid, meso-zeaxanthin, is produced in the retina from lutein according to the research, but also is readily produced by plants and as a result of plant extraction. (Even some supplements that say they only have lutein and zeaxanthin have been shown to also contain meso-zeaxanthin.)

Blood levels of the carotenoids come from the diet or supplementation, but absorption is an issue. Of particular importance is the body’s lipoprotein content – as carotenoids are transported across the blood-brain and blood-eye barriers by lipoproteins. HDL is its most effective transporter, and LDL is the least effective.

This said, mixed supplements also dramatically increase levels of these carotenoids and appear to be readily absorbed.

Mixed carotenoid supplements that include meso-zeaxanthin have been shown to be effective as shown above. The source of the meso-zeaxanthin among these supplements come from plant sources. The most prevalent being the Marigold flower.

Absorption of these nutrients is the critical issue. It is these carotenoids’ hydroxyl functional groups that are able to cross the blood-brain and blood-eye barriers. Other carotenoids, such as beta-carotene or lycopene, cannot cross these barriers.

Nutrition Facts and Analysis for Spinach, raw

Sitting out hunger pangs on a five-day fast

Kale chips

Scientists in California are conducting a clinical trial to test a diet that may help people lose weight while also boosting resistance to some diseases. One of their guinea pigs was the BBC’s Peter Bowes, who reports here on his experience of fasting for five days per month.

It’s been tried on mice and now it’s being tried on humans – a diet that involves multiple five-day cycles on an extremely low-calorie diet. Each of those five days is tough, but the upside is that for much of the time – about 25 days per month – people eat normally, although not excessively.

The low-calorie period includes small amounts of food to minimise the negative effects of a total fast. Designed by scientists to provide a minimum level of essential vitamins and minerals, the diet consists of:

  • vegetable-based soups
  • energy bars
  • energy drinks
  • dried kale snacks
  • chamomile tea
“Start Quote

I was so hungry I would practically lick the soup bowl and shake the last kale crumb from its bag”

These meals are extremely low in calories – about 1,000 on day one and 500 for each of the next four days.

With the exception of water and black coffee, nothing else is consumed.

The limited selection of food (with no choice of flavours) means that everything has to be eaten. It’s monotonous… but at least it makes meal planning easy for five days.

“The reason why diets don’t work is because they are very complicated and people have an interpretation problem,” says Dr Valter Longo, director of the University of Southern California (USC) Longevity Institute.

Spinach soup
Spinach soup: Dinner, three nights out of five

“The reason I think these diets work is because you have no interpretation. You either do it or you don’t do it. And if you do it you’re going to get the effect.”

Dr Longo established a company to manufacture the food, based on research in his department at USC. He has shown in mice that restricting calories leads to them living longer with less risk of developing cancer.

The food used during the trial is the result of years of experimenting. The idea is to develop a diet that leads to positive cellular changes of the same kind seen in mice that have been made to fast.

“It turned out to be a low-protein, low-sugar-and-carbohydrate diet, but a high-nourishment diet,” explains Longo.

“We wanted it to be all natural. We didn’t want to have chemicals in there and did not want to have anything that is associated with problems – diseases. Every component has to be checked and tested. It’s no different to a drug.”

Peter Bowes

Peter Bowes

The popularity of intermittent fasting has grown over the past year or so. The 5:2 diet, which involves dramatically reducing your calorific intake on certain days of the week, is one example. But more clinical data is needed to confirm the benefits of such regimes. Doctors are generally reluctant to recommend them.

Longo stresses that the experimental food could not be made in your kitchen.

But it is a big leap from laboratory mice to human beings. Restricting the diets of rodents is easy, but people have minds of their own – and face the culinary temptations of the modern world.

I knew the diet cycles would be difficult.

I love to eat. I enjoy a big, healthy breakfast, exercise a lot and – left to my own devices – snack all day before digging in to a hearty evening meal. At 51, I am in good shape. I weigh 80kg (12 stone 8lbs / 176lbs) but like most middle-aged men, I struggle with belly fat. I have never tried any kind of fasting regime before.

The diet meals were better than I expected – at least initially. I was so hungry I would practically lick the soup bowl and shake the last kale crumb from its bag, to tide me over to the next feeding time.

Note: it is no longer lunch or dinner. It is a feeding opportunity. It is certainly not a social occasion.

The diet

Day 1 (1,000-1,100 cals) Day 2 (500 cals) Day 3 (500 cals) Day 4 (500 cals) Day 5 (500 cals)
Morning snack Chamomile tea + bar Chamomile tea + bar Chamomile tea + bar Chamomile tea + bar Chamomile tea + bar
Lunch Carrot soup + dried kale Carrot soup + drink Beetroot soup + drink Carrot soup + drink Carrot soup + drink
Afternoon snack Tea + energy bar Tea Tea Tea Tea
Dinner Beetroot soup + dried kale Spinach soup + dried kale Spinach soup + dried kale Beetroot soup + dried kale Spinach soup + dried kale

Headaches, a typical side effect of fasting, started on Day 2 but they waned within 24 hours, leaving me in a state of heightened alertness. During the day – and especially in the morning – I was more alert and productive. Hunger pangs came and went – it was just a matter of sitting them out. But they did go.

Fasting feedback

Alex de la Cruz and Angelica Compos

Alex de la Cruz: I downright hated it. I actually detested it. The first day I had a splitting headache – it felt like someone had punched me in the head. And the weight loss was really dramatic – 4.5kg (10lbs) in the first five days. I was tempted to give up, but I didn’t. After that everything started getting better.

Angelica Campos: There were some positives in being able to be more clear-minded, especially in the morning. I tended to feel worse as the day progressed… I don’t want to do it again, but if someone were to tell me that yes, science proves that it has long-term benefits, I think I would. I need to see proof that it really is effective.

By the evening – especially on Day 5, I was exhausted. Tiredness set in early. But I made it through the five days – for three cycles – without deviating from the regime. I lost an average of 3kg (6.6lbs) during each cycle, but regained the weight afterwards.

All participants keep a diary, noting their body weight, daily temperature reading, meals and mood. The feedback – positive and negative – is vital to the integrity of the study, which is partly designed to establish whether the diet could work in the real world.

For me, and for all but about 5% of the volunteers who have completed all three cycles, the diet was do-able – although opinions vary about the taste of the food.

“It is not an experience for the faint of heart. It was extremely difficult because the little bit of food that you’re offered gets very tiresome as time wears on,” says Angelica Campos, aged 28.

“I had to isolate myself because my family were constantly offering me food. They thought I was crazy.”

She would not want to go through the experience again, but says she would if it were proven to have long-term benefits.

Her boyfriend, Alex de la Cruz, aged 29, says the fasting made him very tired, but when he woke up he was “as alert as could be”.

“My overriding memory of the experience is that the food was horrible, but the results were totally positive,” he says.

Energy bar

Lead investigator Dr Min Wei says that for some people the diet is a greater wrench than for others, depending on their lifestyle. The absence of carbohydrates and desserts, can hit some people hard, for example, and also the restriction to black coffee alone. “We are fairly strict,” he says. “We recommend people stick to the regimen. If people enjoy special coffee – lattes for example – they won’t be able to enjoy them.”

Data from the volunteers is still being collected and analysed. The early signs are that the diet is safe and could be adopted by most healthy people, providing they are suitably motivated to endure the periods of hunger.

But the full effect can only be measured over the long term. Initial changes in the body may not tell the full story.

“Having dietary factors influence your body sometimes takes years and years,” explains Dr Lawrence Piro, a cancer specialist at the Angeles Clinic and Research Institute.

This particular trial now moves into the laboratory. Based on blood tests, has anything changed inside my body to suggest extreme dieting improves my chances of avoiding the diseases of old age?