Google+ Followers

mercredi 23 mars 2016

A rational approach to acid/base balance in humans by L. Fassetto


Theoretically, we humans should be better adapted physiologically to the diet our ancestors were exposed to during millions of years of hominid evolution than to the diet we have been eating since the agricultural revolution a mere 10,000 years ago, and since industrialization only 200 years ago. Among the many health problems resulting from this mismatch between our genetically determined nutritional requirements and our current diet, some might be a consequence in part of the deficiency of potassium alkali salts (K-base), which are amply present in the plant foods that our ancestors ate in abundance, and the exchange of those salts for sodium chloride (NaCl), which has been incorporated copiously into the contemporary diet, which at the same time is meager in K-base-rich plant foods. Deficiency of K-base in the diet increases the net systemic acid load imposed by the diet. We know that clinically-recognized chronic metabolic acidosis has deleterious effects on the body, including growth retardation in children, decreased muscle and bone mass in adults, and kidney stone formation, and that correction of acidosis can ameliorate those conditions. Is it possible that a lifetime of eating diets that deliver evolutionarily superphysiologic loads of acid to the body contribute to the decrease in bone and muscle mass, and growth hormone secretion, which occur normally with age? That is, are contemporary humans suffering from the consequences of chronic, diet-induced low-grade systemic metabolic acidosis? Our group has shown that contemporary net acid-producing diets do indeed characteristically produce a low-grade systemic metabolic acidosis in otherwise healthy adult subjects, and that the degree of acidosis increases with age, in relation to the normally occurring age-related decline in renal functional capacity. We also found that neutralization of the diet net acid load with dietary supplements of potassium bicarbonate (KHCO3) improved calcium and phosphorus balances, reduced bone resorption rates, improved nitrogen balance, and mitigated the normally occurring age-related decline in growth hormone secretion--all without restricting dietary NaCl. Moreover, we found that co-administration of an alkalinizing salt of potassium (potassium citrate) with NaCl prevented NaCl from increasing urinary calcium excretion and bone resorption, as occurred with NaCl administration alone. Earlier studies estimated dietary acid load from the amount of animal protein in the diet, inasmuch as protein metabolism yields sulfuric acid as an end-product. In cross-cultural epidemiologic studies, Abelow found that hip fracture incidence in older women correlated with animal protein intake, and they suggested a causal relation to the acid load from protein. Those studies did not consider the effect of potential sources of base in the diet. We considered that estimating the net acid load of the diet (i. e., acid minus base) would require considering also the intake of plant foods, many of which are rich sources of K-base, or more precisely base precursors, substances like organic anions that the body metabolizes to bicarbonate. In following up the findings of Abelow et al., we found that plant food intake tended to be protective against hip fracture, and that hip fracture incidence among countries correlated inversely with the ratio of plant-to-animal food intake. These findings were confirmed in a more homogeneous population of white elderly women residents of the U.S. These findings support affirmative answers to the questions we asked above. Can we provide dietary guidelines for controlling dietary net acid loads to minimize or eliminate diet-induced and age-amplified chronic low-grade metabolic acidosis and its pathophysiological sequelae. We discuss the use of algorithms to predict the diet net acid and provide nutritionists and clinicians with relatively simple and reliable methods for determining and controlling the net acid load of the diet. A more difficult question is what level of acidosis is acceptable. We argue that any level of acidosis may be unacceptable from an evolutionarily perspective, and indeed, that a low-grade metabolic alkalosis may be the optimal acid-base state for humans.

mercredi 16 mars 2016

MS, sun exposure and vitamin D

Prescribing oral contraceptives in obese women is very dangerous

"The study included 186 cases and 6134 controls. Cases were younger (median age, 40 vs 48 years), more often female (133 [71.5%] vs 3220 [52.5%]), more often used oral contraceptives (97 [72.9%] vs 758 [23.5%] of women), and more frequently had a history of cancer (17 [9.1%] vs 235 [3.8%]) compared with controls. Obesity (BMI ≥30) was associated with an increased risk of CVT (adjusted odds ratio [OR], 2.63; 95% CI, 1.53-4.54). Stratification by sex revealed a strong association between CVT and obesity in women (adjusted OR, 3.50; 95% CI, 2.00-6.14) but not in men (adjusted OR, 1.16; 95% CI, 0.25-5.30). Further stratification revealed that, in women who used oral contraceptives, overweight and obesity were associated with an increased risk of CVT in a dose-dependent manner (BMI 25.0-29.9: adjusted OR, 11.87; 95% CI, 5.94-23.74; BMI ≥30: adjusted OR, 29.26; 95% CI, 13.47-63.60). No association was found in women who did not use oral contraceptives."

In this case-control study that included 186 cases and 6134 controls, obesity was associated with a statistically significant 3-fold increased risk of cerebral venous thrombosis. Stratification by sex revealed that in women who used oral contraceptives, the risk was increased 30-fold. In contrast, we found no association in men or women who did not use oral contraceptives.
Despite those alarming relative risks increases the absolute odd is low however.
This paper is awsome:

Table 1. Overview of differential relative risks of a first VTE for various hormonal contraceptives and HRT

Hormonal contraceptives

Absolute risk (per 1000 person-years)*

HRT, hormone replacement therapy; VTE, venous thromboembolism. *Estimates of the absolute risk were obtained by multiplying the odds ratio with the baseline incidence of VTE of 0.39 per 1000 person-years for women aged 20–44 for hormonal contraceptives, and of 1.00 per 1000 person-years for women aged 45–54 for HRT [3]. †Ethinylestradiol in the most commonly used dose of 30–40 mcg daily. ‡Upper limits of the 95% CIs (10.7 for noresthisterone and 7.1 for injectable depot medroxyprogesterone) do not exclude a strong risk increase. §Inconsistent results from no increased to an increased risk of VTE as compared to oral contraceptives containing norgestimate; no data available of patch users vs. non-users. ¶Upper limit of the 95% CI (3.4) does not exclude a risk increase. **Data from SAE reporting in clinical outcome studies. Wide confidence intervals do not exclude a modest or strong risk increase. ††Upper limit of the 95% CI (1.7) does not exclude a modest risk increase.

Strong risk increase (odds ratio 5–8) [7, 105-107]


2.8 (2.1–3.9)


2.7 (1.8–3.9)


2.5 (1.1–5.3)


2.3 (0.7–8.2)


2.2 (1.4–3.3)


2.2 (1.2–4.0)

Oral progestagen only, high dose (5–30 mg)

2.1 (0.6–7.3)

Moderate risk increase (odds ratio 2–5) [7, 108]


1.5 (0.5–4.1)


1.4 (1.1–1.8)

Injectable depot medroxyprogesterone‡

1.4 (0.7–2.8)

Transdermal ethinylestradiol/norelgestromin§

1.5 (0.5–4.1)

No risk increase [12, 109, 110]

Levonorgestrel releasing IUD

0.1 (0.0–0.4)

Progestagen only, low-dose norethisteron 350 μg or levonorgestrel 30 μg

0.2 (0.1–0.4)

Progestagen only, low-dose desogestrel 75 μg¶

0.2 (0.1–0.7)

Uncertain [111]**

Etonogestrel subcutaneous implant

0.5 (0.01–2.9)

Vaginal ring (ethinylestradiol/etonogestrel)

1.5 (0.1–5.4)


Moderate risk increase (OR 1.5–3.0) [11, 112]

Oral combined estrogen/progestagen pills

2.6 (2.0–3.2)

Oral estrogen only

2.2 (1.6–3.0)

No risk increase [11, 112]

Transdermal (combined estrogen/progestagen and estrogen only) ††

1.2 (0.9–1.7)


0.9 (0.8–1.1)

vendredi 11 mars 2016

Who are we?

In attempting to disentangle fact from scenario, I begin from the beginning, trying to delineate features that may be distinctive of extant humans (ES), and then turning to the fossils that have been included in the species. With the exception of Upper Paleolithic humans - e.g. from Cro-Magnon, Dolni Vestonice, Mladeč - I argue that many specimens regarded as AMS, and all those deemed AS, are not H. sapiens. The features these AMS do share with ES suggest the existence of a sapiens clade. Further, restudy of near-recent fossils, especially from southwestern China (∼11-14.5 ka), reinforces what discoveries such as H. floresiensis indicate: "If it's recent, it's not necessarily H. sapiens".

lundi 7 mars 2016

Sugar and lung cancer in non smokers

Glycemic Index, Glycemic Load, and Lung Cancer Risk in Non-Hispanic Whites

  1. Xifeng Wu1,*
+Author Affiliations
  1. 1Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
  2. 2Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.
  1. *Corresponding Author:
    Xifeng Wu, Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Unit 1340, 1155 Pressler Boulevard, Houston, TX 77030. Phone: 713-745-2485; Fax: 713-792-4657; E-mail:


Background: Postprandial glucose (PPG) and insulin responses play a role in carcinogenesis. We evaluated the association between dietary glycemic index (GI) and glycemic load (GL), markers of carbohydrate intake and PPG, and lung cancer risk in non-Hispanic whites.
Methods: GL and GI were assessed among 1,905 newly diagnosed lung cancer cases recruited from the University of Texas MD Anderson Cancer Center (Houston, TX) and 2,413 healthy controls recruited at Kelsey-Seybold Clinics (Houston, TX). We assessed associations between quintiles of GI/GL and lung cancer risk and effect modification by various risk factors. ORs and 95% confidence intervals (CI) were estimated using multivariable logistic regression.
Results: We observed a significant association between GI [5th vs. 1st quintile (Q) OR = 1.49; 95% CI, 1.21–1.83; Ptrend <0 .001="" and="" cancer="" gi="" lung="" risk="" style="border: 0px; font-size: 0.85em; font-style: inherit; font-weight: inherit; line-height: 0; margin: 0px; outline-style: none; padding: 0px; text-align: inherit;" sub="">ac
 (5th vs. 1st Q OR = 1.48; 95% CI, 1.20–1.81; Ptrend = 0.001) and lung cancer risk. We observed a more pronounced association between GI and lung cancer risk among never smokers (5th vs. 1st Q OR = 2.25; 95% CI, 1.42–3.57), squamous cell carcinomas (SCC; 5th vs. 1st Q OR = 1.92; 95% CI, 1.30–2.83), and those with less than 12 years of education (5th vs. 1st Q OR = 1.75; 95% CI, 1.19–2.58, Pinteraction = 0.02).
Conclusion: This study suggests that dietary GI and other lung cancer risk factors may jointly and independently influence lung cancer etiology.
Impact: Understanding the role of GI in lung cancer could inform prevention strategies and elucidate biologic pathways related to lung cancer risk. Cancer Epidemiol Biomarkers Prev; 25(3); 532–9. ©2016 AACR.

For general practitioners:
"smoking cessation, decreased radon exposure, and in patients with significant smoking history, possible enrollment in a lung cancer screening program"