Instalment 3: Eat less of certain foods

Eat less of animal-based foods

Eating less animal-based foods is part of a strategy of dietary methionine restriction (MR). MR has been found to be effective at treating certain cancers. In addition, in experimental animals it has been found to be as effective as caloric restriction (CR) in increasing healthy lifespan¹. Paradoxically, MR increases appetite and food intake², while at the same time increasing energy expenditure (EE)³ resulting in weight loss overall⁴.

How does MR work? Again, it appears to reduce insulin and IGF-1 signalling⁵.

How would we go about reducing methionine intake?

Animal products are highest in methionine content, both because animal proteins have a relatively high percentage of methionine, and because their protein content is usually also high. Nuts are next highest, followed by grains and legumes. Other vegetables are lower, and fruits are the lowest of all. The range goes from 1 mg methionine per 100 g of apple, to over 1000 mg per 100 g for beef and parmesan cheese. Thus, MR typically involves a vegan-type diet. In fact, it has been proposed that the beneficial effects of vegetarian diets on health may be due to their inherent methionine restriction⁶.

You may have identified a paradox here. If you’ve ever looked into how to lose weight, you’re likely aware of low-carb, or ketogenic diets. Since dietary carbohydrates are the most important stimulant of insulin secretion, these diets have been shown to be effective for weight loss and even for reversing type 2 diabetes. How to reconcile that with the inevitable high carb intake on a methionine restriction diet? Because in spite of all those carbs, methionine restriction lowers insulin levels and causes weight loss in overweight experimental animals. It also did so for me.

I don’t have the answer, but I do have a theory. What if methionine restriction diets stimulated bacteria in the duodenum and small intestine to take up and metabolize the glucose from all those carbs? Then this glucose would not be available for absorption by the animal, and thus would not stimulate insulin secretion. While this theory fits the facts, it’s hard to demonstrate because it’s technically difficult to get at the duodenal or small intestine microbiome.

Whatever the mechanism, methionine restriction lowers insulin and therefore will reduce inflammation.

Eat less protein

Yet another dietary approach to extending healthy lifespan is reducing protein intake. Studies in insects and mice have shown that low protein, high carbohydrate diets are associated with longest lifespan in ad libitum fed animals⁷. In humans, low protein diets reduce the risk for cancer and overall mortality in the population aged ≤65⁸. Dietary protein restriction in elderly patients with chronic kidney disease results in a slower decline in kidney function⁹. Anti-inflammatory effects¹⁰ and improved brain functioning¹¹ have also been demonstrated. As for other anti-inflammatory strategies, it lowers insulin levels¹².

Eat less fruit

Why avoid fruit? Everyone says eat more fruit and vegetables, as if they are somehow the same. But think about this: in most parts of the world, fruit is only available two times a year: in the spring when certain berries ripen (think strawberries) and again in the fall. If you’re a hibernating bear, this is perfect; you wake from your long winter nap, very lean and oh-so-hungry, and you can gorge on those fruits to rapidly regain weight. And in the fall, all that fruit is helpful to build up your fat stores to get you through the winter. We’re not bears, but in primitive societies survival may still be based on putting on weight rapidly from eating fruit.

And this is because fructose (fruit sugar) results in 2 to 3 times higher insulin levels than an equivalent amount of glucose¹³. Because insulin is necessary for fat cells to store fat, this evolutionary adaptation works well for the bear. But, appreciable amounts of fruit or fruit juice (or smoothies) every day may cause chronically high insulin levels.

Unfortunately, most research looking at the effects of plant-based diets lumps fruit and vegetable consumption together, but there are some studies looking at individual effects. Examples: a review found that increased intake of vegetables, but not fruit, was associated with decreased risk of hepatocellular carcinoma¹⁴. Another review reported that dietary vegetable rather than fruit intake was associated with 55% reduced risk of “Barrett’s Esophagus”¹⁵, a condition which may precede adenocarcinoma of the esophagus. More specifically, higher fresh fruit consumption was found to be associated with increased risk of colorectal cancer¹⁶.

With respect to mental health, a review concluded “Increased F&V consumption has a positive effect on psychological well-being and there appears to be a preferential effect of vegetables (compared with fruit) from the limited data examined”¹⁷.

However, there is also evidence that fruit consumption provides health benefits. Fruit is not only fructose; it also has fibre, various antioxidants, and probably microRNA affecting the gut microbiome. So for example, dried fruit consumption is found to be associated with lower cancer incidence or mortality¹⁸.

When considering various dietary sources of fructose, it’s very clear that products containing high-fructose corn syrup, including sugar-sweetened beverages, are bad for your health. At lower consumption levels, fruit is associated with reduced mortality from a variety of conditions, but at higher intakes, the benefit disappears¹⁹.

My advice, then, would be to eat only fresh, unprocessed fruit, so as to maximize benefit from fibre and microRNAs, and to not eat it too often or in large quantities.

Fewer sweet vegetables

As for fruits, some vegetables, eg red beets, carrots, sweet onions, sweet red peppers, or sweet potatoes, are relatively high in fructose content. On the other hand, their content of fibre, antioxidants, and microRNAs may outweigh any negative effects from the fructose load.

End of instalment 3

The next instalment looks at beneficial beverages and at things you should try to eliminate from your diet…

1. Perrone CE, Mattocks DA, Plummer JD et al. Genomic and metabolic responses to methionine-restricted and methionine-restricted, cysteine-supplemented diets in Fischer 344 rat inguinal adipose tissue, liver and quadriceps muscle. J Nutrigenet Nutrigenomics. 2012;5:132-157. PMID 23052097 ↩
2. Orentreich N, Matias JR, DeFelice A, Zimmerman JA. Low methionine ingestion by rats extends life span. J Nutr. 1993;123:269-274. PMID 8429371 ↩
3. Plaisance EP, Greenway FL, Boudreau A et al. Dietary methionine restriction increases fat oxidation in obese adults with metabolic syndrome. J Clin Endocrinol Metab. 2011;96:E836-40. PMID 21346062 ↩
4. Perrone CE, Mattocks DA, Plummer JD et al. Genomic and metabolic responses to methionine-restricted and methionine-restricted, cysteine-supplemented diets in Fischer 344 rat inguinal adipose tissue, liver and quadriceps muscle. J Nutrigenet Nutrigenomics. 2012;5:132-157. PMID 23052097 ↩
5. Perrone CE, Mattocks DA, Plummer JD et al. Genomic and metabolic responses to methionine-restricted and methionine-restricted, cysteine-supplemented diets in Fischer 344 rat inguinal adipose tissue, liver and quadriceps muscle. J Nutrigenet Nutrigenomics. 2012;5:132-157. PMID 23052097 ↩
6. McCarty MF, Barroso-Aranda J, Contreras F. The low-methionine content of vegan diets may make methionine restriction feasible as a life extension strategy. Med Hypotheses. 2009;72:125-128. PMID 18789600 ↩
7. Simpson SJ, Le Couteur DG, Raubenheimer D et al. Dietary protein, aging and nutritional geometry. Ageing Res Rev. 2017;39:78-86. PMID 28274839
   Le Couteur DG, Solon-Biet S, Cogger VC et al. The impact of low-protein high-carbohydrate diets on aging and lifespan. Cell Mol Life Sci. 2016;73:1237-1252. PMID 26718486 ↩
8. Levine ME, Suarez JA, Brandhorst S et al. Low protein intake is associated with a major reduction in IGF-1, cancer, and overall mortality in the 65 and younger but not older population. Cell Metab. 2014;19:407-417. PMID 24606898 ↩
9. Bernier-Jean A, Prince RL, Lewis JR et al. Dietary plant and animal protein intake and decline in estimated glomerular filtration rate among elderly women: a 10-year longitudinal cohort study. Nephrol Dial Transplant. 2021;36:1640-1647. PMID 32457981 ↩
10. Kim HJ, Vaziri ND, Norris K, An WS, Quiroz Y, Rodriguez-Iturbe B. High-calorie diet with moderate protein restriction prevents cachexia and ameliorates oxidative stress, inflammation and proteinuria in experimental chronic kidney disease. Clin Exp Nephrol. 2010;14:536-547. PMID 20820841 ↩
11. Wahl D, Solon-Biet SM, Wang QP et al. Comparing the Effects of Low-Protein and High-Carbohydrate Diets and Caloric Restriction on Brain Aging in Mice. Cell Rep. 2018;25:2234-2243.e6. PMID 30463018 ↩
12. Zhang X, Qiu K, Wang L, Xu D, Yin J. Integrated Remodeling of Gut-Liver Metabolism Induced by Moderate Protein Restriction Contributes to Improvement of Insulin Sensitivity. Mol Nutr Food Res. 2018;62:e1800637. PMID 30030886 ↩
13. Chee, Melissa. Fructose and the Hungry Brain. Seminar, McGill University, 2020-2-14.
    Fructose is a simple sugar found in fruit and honey, but it is also used as sweeteners via added sugars, syrups, or high fructose corn syrup in processed foods or beverages. This is a concern because excessive fructose intake is linked to obesity and its comorbid diseases like diabetes and cardiovascular disease. We show that mice consuming a high fructose diet eat more and gain more weight and body fat than mice consuming chow or a high glucose diet. As the brain is a vital organ mediating the actions of fructose, we determined the neuronal maladaptations underlying fructose-mediated obesity. Interestingly, fructose feeding increased excitatory drive to hypothalamic neurons known to stimulate food intake, and this excitatory drive is comparable to that seen during hunger. This presentation will examine the synaptic plasticity and whether it may be reversed with the cessation of fructose feeding. Our findings indicate that central maladaptations following excessive fructose consumption may contribute to overeating and the development of diet-induced obesity. ↩
14. Yang Y, Zhang D, Feng N et al. Increased intake of vegetables, but not fruit, reduces risk for hepatocellular carcinoma: a meta-analysis. Gastroenterology. 2014;147:1031-1042. PMID 25127680 ↩
15. Zhao Z, Pu Z, Yin Z et al. Dietary fruit, vegetable, fat, and red and processed meat intakes and Barrett’s esophagus risk: a systematic review and meta-analysis. Sci Rep. 2016;6:27334. PMID 27256629 ↩
16. Keskin H, Wang SM, Etemadi A et al. Colorectal cancer in the Linxian China Nutrition Intervention Trial: Risk factors and intervention results. PLoS One. 2021;16:e0255322. PMID 34525122 ↩
17. Tuck NJ, Farrow C, Thomas JM. Assessing the effects of vegetable consumption on the psychological health of healthy adults: a systematic review of prospective research. Am J Clin Nutr. 2019;110:196-211. PMID 31152539 ↩
18. Mossine VV, Mawhinney TP, Giovannucci EL. Dried Fruit Intake and Cancer: A Systematic Review of Observational Studies. Adv Nutr. 2020;11:237-250. PMID 31504082 ↩
19. Kazemi A, Soltani S, Mokhtari Z et al. The relationship between major food sources of fructose and cardiovascular disease, cancer, and all-cause mortality: a systematic review and dose-response meta-analysis of cohort studies. Crit Rev Food Sci Nutr. 20211-14. PMID 34847334 ↩

• ← Instalment 2: Dietary interventions
• Instalment 4: About beverages, and things to try to eliminate from your diet →