A body of research known as caloric restriction is providing additional findings that support the fact that it is ultimately, the quality and quantity of carbohydrates, fats, and proteins that determine the "biochemical" health and vitality of an individual. In fact, to date it is the only scientifically proven method known to increase both the median (up to 40%) and maximal (up to 20%) lifespan. In the research that follows, one will see that nutritional and/or herbal supplementation, though it may alleviate symptoms and even help ward off or delay life-threatening complications of many disease processes (e.g., the benefits of Vitamin C as it relates to cardiovascular disease), does not correct the underlying cause of disease, nor has research been able to demonstrate life extension benefits from nutritional and/or herbal supplementation.
Comment: I'm not down on nutritional and herbal supplements, but simply bringing a greater understanding as to their benefits and limitations in relation to "nutritious" whole foods. From the nutritional standpoint, when it comes to whole foods, the whole is greater than the sum of its parts. And, though science will never duplicate nature, it can give us a greater appreciation for it. With that said, "moving" in the direction of making better dietary choices should be the first and primary consideration for normalizing physiology. All it takes are good scientific reasons to do so and trusting the innate make-up of our being and the living experience.
The research in caloric restriction has been concerned almost exclusively with decreasing the daily caloric intake of macronutrients (carbohydrates, fats, and proteins) by 30% to 50% without addressing the quality or source. This has been addressed primarily by decreasing the quantity of carbohydrate. Some studies have addressed the quantity and to a lesser extent the quality of fats (primarily corn oil vs. fish oil (omega-3) with the exclusion of most other oil sources, e.g., coconut, olive, avacado, etc. To date, proteins have rarely been addressed. Again, though not addressed, the source and quality of macronutrients are extremely important. Just one reason being that the foods that are less dense in macronutrients typically contain greater quantities of micronutrients (vitamins, minerals, antioxidants, etc.). Therefore, not only are they supplying more nutrition, but also the ratio of micronutrient to macronutrient increases significantly. Never the less, the results seen with caloric restriction are impressive.
Benefits Resulting from Caloric Restriction
More efficient aerobic metabolism as seen with a decrease in oxidative stress and a concurrent increase in antioxidant stores.
Decreased oxidative damage of CNS with increased neural integrity;
Enhanced immune function;
Improved DNA synthesis and repair;
Increased hormonal efficiency, such as GH, insulin, and thyroxin;
Increased ability to detoxify by way of the liver and kidneys;
Increased nutrient absorption by as much as 80%;
Normalization and maintenance of optimum body weight;
Aging, Disease and Caloric Restriction
Prevention and reversal of age related dementia and other diseases of the CNS
Caloric restriction of carbohydrates have shown a number of very positive effects on age-related functions of the CNS, such as a 2-fold improvement in learning, memory, synaptic population responses, long term potentiation, and sensorimotor coordination. In addition, caloric restriction has demonstrated increased resistance of neurons to dysfunction and death in experimental models of diseases such as Alzheimer's, Parkinson's, Huntington's, seizures, and strokes. The underlying mechanism is believed to involve stimulation of the expression of "stress proteins" and neurotrophic factors that suppress oxyradical production, stabilize cellular calcium, and inhibit apoptotic biochemical cascades. Caloric restriction also increases the number of newly generated neural cells in the adult brain indicating that caloric restriction increases the brains capacity for plasticity and self-repair.
Comment: The CNS does not require insulin for the uptake of glucose. Therefore, it is very poor at regulating the amount of neuronal exposure to glucose making glucose a potential and potent irritant. Many of the "diseases" of the CNS either result from, or are exacerbated by, carbohydrate stress on CNS (Pattern 7).
Combating infectious disease without inflammation
A 25% calorie restricted diet compared to a normal diet cleared streptococcus infection within 24 hours without an inflammatory response, where as the normal fed group experienced a prolonged infection. In another study of ulcerative skin lesions, 89% of the mice fed a normal diet died from septicemia, while only 33% of the 40% caloric restricted group developed such lesions and those that did develop lesions survived twice as long, Perkins, et al., (1998).
Zaloga and Roberts, (1994) found that nutritional therapies that maximize nitrogen balance, that is, more protein than is required for the daily functions of repair, growth, and homeostasis, adversely affect the host's response to injury and infection.
Comment: The adverse effect of excessive or "dense or poor quality" protein is due, in part, to a number of physiologic stresses. For example, increased protein intake can depress thyroid function (Pattern 2), impair growth hormone secretion, and place unwanted stress on the lymphatic system, all of which result in impaired healing and immune responses.
Effects of caloric restriction on myocardial health
40% caloric restriction limited oxidative stress and inflammatory responses of ischemic myocardium as seen by rapid recovery of GSH levels, a transient expression of cytokines, interleukin-1, and tumor necrosis factor as compared to the normal fed group. Chandraeekar, et al., (2001) concluded that caloric restriction significantly attenuates myocardial oxidative stress and the post-ischemic inflammatory response. In addition, Van Liew, et al., (1992) found that 40% caloric restriction prevented the age-dependent increase of microalbuminuremia, an early marker for coronary disease and nephropathy (Pattern 3).
Comment: Most, if not all, inflammatory responses respond favorably to decreasing carbohydrates (Pattern 5) and to a lesser extent to increasing EPA. However, clinically we have found that what initiates the myocardial infarction is a decrease in CO2 either from an increase in blood protein or mental/emotional stress, especially one of hopelessness. This is due to the fact that a decrease in CO2 (as seen in hyperventilation) causes a decrease in calcium as well as an autonomic vasoconstriction of the coronary arteries, (Pattern 3).
Caloric restriction and oil sources in autoimmune responses
There have been a number of studies comparing caloric restriction supplemented with fish oil vs. corn oil and their effects on autoimmune responses relating to lupus and other diseases. These studies have demonstrated that autoimmune markers, such as PDGF-A, thrombin receptor, cytokines, and T lymphocytes, rise in the normal corn oil fed mice, decrease slightly in the normal fish oil fed mice, decrease significantly in the caloric restricted corn oil fed mice, and are absent or decrease to levels seen in young animals in the caloric restricted fish oil fed mice.
Comment: EPA (a precursor for series 3 prostaglandins) is necessary for the anti-inflammatory response, and humans are very inefficient at producing EPA, thus making dietary sources, such as nori, very important. However, the research shows that the greatest results with inflammation are achieved by decreasing carbohydrates more so than EPA supplementation, (Pattern 5).
Carcinogenesis and promotion
In a number of studies of breast, skin, liver and colon carcinogenesis and promotion, it was found that 20-40% caloric restriction of both fats (typically low quality fats, such as corn oil) and carbohydrates inhibited both onset and progression of cancer as much as 70%. Comparing fish oil to corn oil fed animals, fish oil showed significantly less tumor onset and promotion with survival rates greatly exceeding those of the corn oil fed animals. In addition, animals with radiation-induced solid tumors and myeloid leukemias showed a significant delay in onset and prolongation in lifespan whether caloric restriction was initiated before, or after, tumors were induced with radiation (Yoshida, et al., 1997); Koohestani, et al., (1998); Birt, et al., 1991; Kumar, et al., (1990).
Comment: 60% of the fatty acids found in corn oil consist of linoleic acid, an omega-6 fatty acid, the precursor for arachadonic acid and series 2 prostaglandins. Therefore, corn oil, in a "compromised" metabolic environment (due to poor quality and quantity of carbohydrates) promotes inflammation...the body's ability to initiate healing being dependent on the anti-inflammatory response.
Decrease oxidative stress on mitachondrial membranes and DNA
There have been numerous studies on caloric restriction demonstrating a decrease in oxidative damage with a not surprisingly increase in antioxidants, many times the levels of antioxidants in the aged equaling or exceeding those of the young. Most researchers in this area are focusing on the integrity and function of the mitochondria as it relates to the mitochondrial membrane and mitochondrial DNA. Weindruch, et al., (2001) used high-density oligonucleotide arrays representing 6347 genes and concluded that aging resulted a differential gene expression pattern indicative of lower expression of metabolic and biosynthetic genes, and that caloric restriction completely or partially prevented most of the aberrations. Haley-Zitlin and Richardson, (1993) found that not only was repair of DNA damage higher with caloric restricted diets, but the levels of DNA damage was reduced as well.
Non-Human Primate Studies
In an ongoing study, Hansen, et al., (1999) reports that caloric restriction of adult monkeys significantly reduced morbidity and increased the median lifespan. After 15 years of caloric restriction, monkeys, now 25 years old, are exceeding the median lifespan of the controls, the maximum lifespan being approximately 40 years old. Weed, et. al., (1997) has found that monkeys after 6 years of caloric restriction demonstrated increased motor activity, open field behavior, and grooming compared to controls. These increases in activity are consistent with those of rodent studies. Other studies on non-human primates have also demonstrated increased insulin responsiveness, decreased LDL, and lower fasting glucose levels than the controls.
Human Studies
Inhibition of tumor initiation and progression of malignancies of the breast, skin, and colon
In a study comprised of 2569 women with breast cancer (median age of 55) and 1953 men and women with colorectal cancer (median age of 62) and 5155 hospital controls followed for 5 years found significant trends of increased risk for colorectal and breast cancer with increased intake of starch and saturated fats (i.e., long-chain saturated fatty acids). Most vegetables and fruits were inversely associated with colorectal cancer, where as only carrots and raw vegetables seemed to lower breast cancer risk. Of the fats studied, olive oil was found to be the most protective, (Franceschi and Favero, 1999).
Comment: Coconut oil, comprised of short and medium chain saturated fatty acids, was not considered. In upcoming papers, the beneficial role of short and medium-chain fatty acids vs. long chain fatty acids will be discussed in relation to immune responses, thyroid and liver function, inflammation, skin health, etc.
Biosphere inhabitants
Biosphere 2 is an ecosystem that is energetically open (sunlight, electricity, and heat), but material closed with air, water, and organic material being recycled. It has housed four men and four women since September 1991. Their diet is low in calorie (averaging 1780 kcal/day) and nutrient dense. Significant reductions were noted in leukocytes [6.7 to 4.7 x 10(9)], blood pressure, fasting glucose, cholesterol, triglycerides, HDL (risk ratio was unchanged), and males averaged a 16% reduction in weight, and women averaged an 11% reduction. Wallford, et al., (1999) concluded that these results clearly suggest that humans react to caloric restriction similarly as other vertebrates.
Comment: With caloric restriction, one sees a decrease in hormonal levels (in laboratory animals due to lack of activity), blood glucose, triglycerides, cholesterol, VLDL, LDL, and HDL. Along with that is an increase in absorption of nutrients by as much as 80%, Casirola, et al., (1996). A more efficient system should be more efficient at even nutrient absorption as nutrient uptake is simply another "normal" physiologic function of all cells, see Growth Hormone:Somatostatin Axis.
Proposed Theories Concerning Caloric Restriction
Reduced oxidative stress on the mitochondria
Much of the research concerning caloric restriction is focusing on the free radical theory and mitochondrial function as it relates to ATP production. ATP production, being the primary oxidative process of a cell, exposes the mitochondria and its DNA to substantial oxidative stress. Over time, especially with an increase in metabolic demand, the oxidative processes of ATP production causes an accumulation of free radicals, especially within the inner mitochondrial membrane where ATP production takes place. This accumulation can then directly affect, not only the structural and functional components of the cell, but even the DNA.
Antioxidant supplementation
Meites, (1993) and others have looked at the effects of antioxidant supplementation as it relates to the most popular theory of longevity and the prevention of disease. One would expect to see some correlation between supplying antioxidants and slowing of the aging process. To date there has not been a single study that has demonstrated life extension benefits, nor significantly delaying or reversing declines in physical or mental function due to the "aging process" in mammals as a result of antioxidant supplementation. This suggests, along with other considerations and studies, that the beneficial effects (anti-aging and disease prevention) of caloric restriction are more encompassing than merely reducing oxidative stress.
Comment: The mitochondria are concerned with much more than just ATP production, as it is the role of the citric acid cycle to supply substrates necessary to fulfill the energy, structural, functional, and storage needs of the cell. In fact, the citric acid cycle is the pivotal point for many, if not most, of the pathways concerned with the metabolic functions of the cell. For example, fatty acid synthesis is initiated from citrate; protein synthesis from a-ketogluterate and oxaloacetate; heme from succinyl Co-A; and hydrogen for entry into the electron transport chain are just a few. It is the electron transport chain that is responsible for 90% of the ATP produced by the cell. And, while ATP production does create damaging free radicals, free radicals are not the only irritants to cellular function as it relates to disease and aging. Any aspect of cellular metabolism that places undue stress on the citric acid cycle can ultimately be detrimental to our health and vitality. Increased oxidative stress and a deficiency of antioxidants hold no more or no less importance than any other biochemical process.
Neuroendocrine
The anti-aging effects of hormones can be seen when hormones such as growth hormone, testosterone, or progesterone are administered to the aged. An increase in hormones in this instance promotes gene expression, elevates protein synthesis, and enhances metabolism, growth, and function of most organs and tissues. That is, hormones can improve the quality of life by supporting the anabolic processes of metabolism, though they (hormones) do not actually extend life. On the other hand, the aging effects of hormones are demonstrated when a reduction in hormonal secretion (in the sedentary laboratory animal), due to caloric restriction, results in slowing of the aging process, and the suppression or prevention of chronic disease. Administration of hormones in this instance counteracts or negates the positive effects of caloric restriction, leading some researchers to believe that the favorable effects of aging are due to the neuroendocrine systems.
Hormonal supplementation
Hormonal supplementation is drawing increased public attention as a means of decreasing or preventing disease and delaying the onset of aging. Pugh, et al., (1999) divided 300 mice into four groups and evaluated them for longevity and spontaneous disease patterns. Group 1 and 2 were fed normal diets (ND) and groups 3 and 4 were fed caloric restricted diets (CR). One (ND) group and one (CR) group were given 25 microgm/ml DHEA in their water. Although DHEA supplemented mice showed a 10-fold increase in DHEA over the non-supplemented groups, DHEA supplementation did not influence weight, cancer patterns, or lifespan when compared to their dietary equivalent.
Comment: The hypothalamus, pineal, and area postrema are the only structures of the CNS that do not have a blood brain barrier. The hypothalamus, being in direct contact with the vascular system, not as much controls, but mediates most vegetative functions of the body as well as many aspects of emotional behavior. It is the quality and quantity of proteins, fats, and carbohydrates that ultimately determine the direction physiology must take, often at the expense of the neuroendocrine system. One example of this is seen in the relationship or "negative" influence that (digestive and assimilative) have on (hormonal and neurotransmitter). For example, excessive carbohydrate intake pushes cellular metabolism to produce cholesterol (Pattern 5) at the expense of the androgen (anabolic) hormones (Pattern 8). In this instance, exogenous (prescription or herbal) hormonal support can alleviate symptoms and some of the dis-ease due to their anabolic effects on a physiology that is compromised. However, it is obviously more advantageous to work within the normal limits of physiology for greater health and wellbeing than to rely on excessive hormonal support to sustain a less than healthy metabolic push. On the other hand, as seen with caloric restriction there is a decrease in the degree of metabolic push. Administration of hormones in this instance begins to once again push metabolism, thus negating the positive effects of caloric restriction.
Note: A point that has not been considered with caloric restriction, but will be covered in detail in subsequent papers, is exercise. In just the past few months we have come to a new understanding as to what it means to exercise within optimum healthy limits with intensity, and the profound effects it can have on all aspects of our being. It is a methodology that produces little or no anxiety or mental/emotional resistance to exercise with amazing results and health benefits.
References
Mech Aging Dev, 79(1): 33-57
Lipman RD et al., Aging (Milano) 10(6): 463-70
Lipman RD et. al., Aging (Milano) 7(2): 136-9
Van Remmen H et al., Novartis Found Symp 235: 221-30
Lipman RD et al., The Journals of Gerontology 54(11): B478-B491
Nelson JF et al., Neurobiol 16(5): 847-43
Everitt A et al., J Gerontol 44(6): B139-47
Journal of Nutritional Science and Vitaminology, 47(1): 13-19
Meites J, Proc Soc Exp Biol Med 195(3): 304-11
Razzaque MS et al., Biochemical and Biophysical Research Communications 1(1): 82-85
Kobayashi S et al., Kidney Int 42(3): 710-7
De Tata V et al., Exp Gerontol 36(3): 507-18
Siciliano et al., Journal of Animal Science78(12): 3107-3113
Powell D et al., Equine Vet j Supp0: 514-8
Ramsey JJ et al., Free Radic Biol Medf 29(10): 946-68
Murtagh-Mark CM et al., J Gerontol A biol Sci Med Sci 50(3): B148-54
Scrofano MM et al., Mechanisms of Aging and Development101(3): 277-296
Scrofano MM et al., Mech Ageing Dev105(1-2): 31-44
Duffy PH et al., Chronobiol Int 7(2): 113-24
Shanley DP et al., Evolution Int J Org Evolution 54(3): 740-50
Hansen BC et al., Toxicol Sci 52(2 Suppl): 56-60
Weed JL et al., Physiology and Behavior 62(1): 97-103
DeLaney JP et al., J Gerontol A Biol Sci Med Sci 54(1):B5-11
Kayo T et al., Proc Natl Acad Sci USA 98(9): 5093-8
Ramsey JJ et al., Exp Gerontol 35(9-10): 1131-49
Black A et al., J Gerontol A Bio Sci Med Sci 2001 Mar 56(3): B98-107
Pendergrass WR et al., J Cell Physiol180(1): 123-30
Bodkin NL et al., J Gerontol A Biol Sci Med Sci 50(3): B142-7
Ortmeyer HK et al., j Basic Clin Physiol Pharmacol 9(2-4): 309-23
Clark A et al., Diabetes, 50 Suppl 1: S169-71
Kritchevsky D Cancer 66(6 Suppl): 1321-5
Quigley K et al., Neurobiol Aging 8(3): 225-32
Engelman RW et al., Cancer Res 54(21): 5724-30
Poetschke HL et al., Carcinogenesis 21(11): 1959-64
Freni SC et al., Cancer Causes Control 7(3): 358-65
Walford RL et al., J Gerontol A Biol Sci Med Sci 52(4): B179-83
Walford, Roy L et al., Toxicological Sciencea (online) 52(2): 61-65
Walford RL et al., Proc Natl Acad Sci USA 89(23): 11533-7
Life Sciences 2000 (New York, N.Y.) 66(16): 1471-1480
Casirola DM et al., Am J Physiol 271(1 PT 1): G192-200
Casirola DM et al., J Gerontol A Biol Sci Med Sci 52(6): B300-10
Pugh TD et al., Cancer Res 59(7): 1642-8
Meites J, J Reprod Fertil Suppl 46: 1-9
Doubal S et al., Age 22(3): 101-106
Zaloga GP et al., New Horiz 2(2): 257-63
Kritchevsky D, Eur J Cancer Prev 4(6): 445-51
Gillette CA et al., Carcinogenesis 18(6): 1183-8
Lambert AJ et al., Exp Gerontol 35(5): 583-94
Sanderson JP et al., J Gerontol A Biol Sci Med Sci 52(1): B20-5
Georgette JC et al., Arquivos Brasileiros 72(4a): 431-440
Peck MD et al., J PEN J Parenter Enteral Nutr 16(6): 561-5
Ruhe RC et al., Aging (Milano) 8(4): 287-91
Expermental Gerontology 1997 32(1-2): 205-214
Goya RG et al., Neuroendocrinology 51(1): 59-63
Katzeff, Harvey L et al., American Journal of Physiology 273(5-1): E951-E956
Harvey J et al, American Journal of Physiology 23(2): 105-15
Choi JH et al., 4(3): 182-6
Brain Research 886(1-2): 47-53
Hori N et al., 3(12): 1085-8
Dubey A et al., 333(1): 189-97
Bough KJ et al., 35(1): 21-8
Joseph JA et al., 16(4): 607-12
Bough KJ et al., 38(2-3): 105-14
Mhatre et al., 54(2): 270-275