ALSUntangled #73: Lion's Mane.

Lion's Mane (Hericium erinaceus) has historically been used as traditional medicine in Asia and Europe for its potential benefits in fighting infection and cancer. It has gained interest in the neurodegenerative disease field because of its mechanisms of action; these include anti-inflammation, neuroprotection, and promoting neurite growth demonstrated in various cell and animal models. A very small, double-blind, placebo-controlled trial in patients with mild cognitive impairment showed a temporary improvement in cognitive function; this finding has yet to be replicated. However, there have been no studies in ALS cell or animal models or in humans with ALS. Lion's Mane appears safe and inexpensive when consumed in powder or capsule, but one anaphylactic case was reported after a patient consumed fresh Lion's Mane mushroom. Currently, we do not have enough information to support the use of Lion's Mane for treating ALS. We support further research in ALS disease models and clinical trials to study its efficacy.

ALSUntangled #72: Insulin.

ALSUntangled reviews alternative and off-label treatments for people living with amyotrophic lateral sclerosis (PALS). Here we review insulin, which has at least one plausible mechanism for slowing ALS progression. However, pre-clinical studies are limited and there have been no trials in PALS yet. Insulin use in patients without a metabolic need may cause very serious and potentially lethal side effects. While further studies to evaluate potential benefits may be warranted, at this time we cannot endorse insulin treatment to slow ALS progression.

The effects of receiving diet roughage inclusion on performance, health, and serum metabolite characteristics of newly received beef calves.

Current dogma suggests increased dietary roughage may improve calf health at the expense of performance during receiving. In experiment 1, the effects of increasing dietary roughage on performance and clinical health of high-risk heifers was evaluated over a 56-d receiving period. Heifers (n = 589; initial body weight; BW = 230 ±â€…33 kg) were sourced from Oklahoma livestock auctions from April through October of 2019. Heifers were randomly assigned to pens, which were randomly assigned to 1 of 3 experimental dietary treatments in a randomized complete block design. Diets contained either: 1) 15% roughage (R15), 2) 30% roughage (R30), or 3) 45% roughage (R45) in the form of prairie hay. Orthogonal contrasts were used to test for linear and quadratic responses among experimental treatments. There was a linear decrease in overall average daily gain (ADG; P ≤ 0.0001) with increasing roughage inclusion which resulted in a linear decrease (P ≤ 0.0001) in heifer final BW. A linear increase (P ≤ 0.01) was observed for overall dry matter intake (DMI), and overall gain:feed (G:F) decreased linearly (P ≤ 0.0001) as dietary roughage concentration increased. A quadratic response to decreasing roughage was observed (P = 0.02) for the percent of calves treated three times for bovine respiratory disease (BRD). No other responses (P ≥ 0.11) were detected in animal health variables. In experiment 2, Angus steers (n = 12) and heifers (n = 6; BW = 272 ±â€…28 kg) were acquired from a single ranch in Oklahoma to evaluate the same experimental dietary treatments on serum metabolite concentrations. Animals were randomly assigned to experimental treatments, with animal serving as the experimental unit in experiment 2. Statistical models for serum metabolites in experiment 2 were analyzed using repeated measures with the effects of treatment, time, and treatment × time. In experiment 2, there were tendencies for treatment × time interactions for blood urea nitrogen (BUN; P = 0.07) and nonesterified fatty acid (NEFA; P = 0.06) concentrations. No metabolites were affected by treatment (P ≥ 0.11), while all metabolites were impacted by time (P ≤ 0.02). In summary, growth performance was improved in calves as dietary roughage concentration decreased with minimal impacts on health and serum metabolites. These results suggest that diets containing as little as 15% roughage can be used during receiving to improve calf performance without compromising calf health when fibrous byproducts are included in the diet.

ALSUntangled #66: antimycobacterial antibiotics.

Several infections have been associated with motor neuron diseases resembling ALS, including species of viruses, bacteria, and parasites. Mycobacterium avium subspecies paratuberculosis (MAP), most known for its probable etiologic association with Crohn's disease, has been suggested as another possible infectious cause of motor neuron disease. Two published case reports describe the successful treatment of ALS-like symptoms with antimycobacterial antibiotics. Both cases had atypical features. Based on these, we believe it would be reasonable to begin performing chest imaging in PALS who have features of their history or exam that are atypical for ALS such as pain, fevers, or eye movement abnormalities. If the chest imaging is abnormal, more specific testing for mycobacteria may be indicated. Until there is more clear evidence of an association between mycobacteria and ALS, we cannot endorse the widespread use of potentially toxic antimycobacterial antibiotics for PALS.

ALSUntangled #68: ozone therapy.

ALSUntangled reviews alternative and off-label treatments for people living with amyotrophic lateral sclerosis (PALS). Here we review ozone therapy. Ozone therapy has possible mechanisms for slowing ALS progression based on its antioxidant, anti-inflammatory, and mitochondrial effects. A non-peer-reviewed report suggests that ozone treatment may slow progression in a mTDP-43 mouse model of ALS. One verified "ALS reversal" occurred on a cocktail of alternative treatments including ozone. There are no ALS trials using ozone to treat PALS. There can be potentially serious side effects associated with ozone therapy, depending on the dose. Based on the above information, we support an investigation of ozone therapy in ALS cell or animal models but cannot yet recommend it as a treatment in PALS.

ALSUntangled #65: glucocorticoid corticosteroids.

ALSUntangled reviews alternative and off-label treatments for people with amyotrophic lateral sclerosis (PALS). Here we review glucocorticoids. Neuroinflammation plays a prominent role in amyotrophic lateral sclerosis (ALS) pathogenesis, so some hypothesize that glucocorticoids might be an effective ALS therapy through their immunosuppressive effects. In this paper, we review the available evidence for glucocorticoids in ALS, including one pre-clinical study with a genetic mouse model of ALS, nine case reports (ranging from 1 to 26 patients each), and four clinical trials. We also review the possible side effects (including steroid myopathy) and the costs of therapy. We graded the level of evidence as follows: Mechanism, D; Pre-Clinical, F; Cases, B; Trials, F; Risks, C. Our review of the current evidence concludes that glucocorticoids do not offer clinical benefit in ALS and confer serious risks. Thus, ALSUntangled does not recommend glucocorticoids as a treatment for ALS.

ALSUntangled #67: rituximab.

ALSUntangled reviews alternative and off-label treatments on behalf of people with ALS who ask about them. Here we review rituximab, a drug which specifically depletes B lymphocytes. We show a current lack of evidence for a role of these cells in ALS progression. The one patient we found who described using Rituximab for their ALS found no benefit. Given all this, and the known serious risks of rituximab, we advise against its use as an ALS treatment.

ALSUntangled #70: caffeine.

ALSUntangled reviews alternative and off-label treatments for people living with amyotrophic lateral sclerosis (PALS). Here, we review caffeine which has plausible mechanisms for slowing ALS progression. However, pre-clinical studies are contradictory, and a large case series showed no relationship between caffeine intake and ALS progression rate. While low doses of caffeine are safe and inexpensive, higher doses can cause serious side effects. At this time, we cannot endorse caffeine as a treatment to slow ALS progression.

Evaluation of ruminal degradability and metabolism of feedlot finishing diets with or without cotton byproducts.

Cotton byproducts can be an economical source of protein, fat, and fiber in cattle finishing diets. The objectives of this study were 1) to assess the effects of including whole cottonseed (WCS) and cotton gin trash (CGT) in finishing diets on in situ ruminal degradability and 2) to determine the effects of including cotton byproducts in a finishing diet on rumen fluid pH, lactate, and volatile fatty acid concentrations. Six ruminally cannulated steers were used in a crossover design. Treatments included a control diet (CON; 7% prairie hay [PH], 15% Sweet Bran, 67.25% rolled corn, and 5% liquid supplement) and a cotton byproduct diet (CTN; 7% CGT, 15% WCS, 72.25% rolled corn, and 5% water). Both diets included 0.75% urea and 5% dry supplement. In situ bags containing individual diet ingredients and whole diet samples were incubated in the rumen for up to 96 h. Rumen fluid samples were collected over a 24-h period. No treatment × substrate interactions were detected for any fraction of dry matter (DM) or organic matter (OM) degradability for individual ingredients or whole diets (P ≥ 0.14). The A, B, and C fractions, disappearance rate (Kd), and effective degradability of DM and OM differed between diet ingredients (P ≤ 0.04) but were not different between CON and CTN substrates (P ≥ 0.25). A treatment × substrate interaction (P = 0.04) was detected for the effective degradability of neutral detergent fiber (NDF) of CGT and PH but there was no interaction for other fractions (P ≥ 0.27). The A fraction of NDF was greater (P < 0.001) for CGT than PH; however, the B fraction of NDF tended to be greater (P = 0.08) for PH than CGT. No differences (P ≥ 0.37) were detected for the % NDF disappearance at 48 h between CON and CTN substrates. A tendency for a treatment × substrate interaction (P = 0.10) was observed for the effective degradability of starch among diets; however, when the CON substrate was incubated in steers consuming the CON diet, effective degradability of starch was not different (P = 0.84) from when the CTN diet was incubated in steers consuming the CTN diet. There was no treatment × time interaction or treatment effect for rumen pH; however, there was a time effect (P = 0.03). Steers consuming the CTN diet had greater molar proportions of acetate and decreased molar proportions of propionate compared with CON steers (P < 0.01). This experiment suggests that there are minimal differences between the digestibility of finishing diets containing cotton byproducts and those comprised of traditional finishing diet ingredients.

Effects of utilizing cotton byproducts in a finishing diet on beef cattle performance, carcass traits, fecal characteristics, and plasma metabolites.

Increased cotton production in the Southwestern United States has increased the availability of cotton byproducts for use in cattle diets. The objective of this experiment was to evaluate the inclusion of cotton byproducts in feedlot finishing diets on the performance, carcass traits, fecal characteristics, and plasma metabolites of steers. Crossbred beef steers (n = 64; BW = 318 ± 12.3 kg) were assigned to 1 of 2 experimental treatments in a randomized complete block design (8 pens per treatment; 4 steers per pen). Treatments included a control (CON) diet, which included prairie hay, Sweet Bran, rolled corn, and a corn steep and molasses-based liquid fat supplement, and a cotton byproduct (CTN) diet, which included cotton gin trash, whole cottonseed, rolled corn, and water. Both diets contained urea and dry supplement. Over the entire feeding period, DMI (P = 0.04) was greater for CTN steers than CON steers with no difference in the gain to feed ratio (P = 0.86) between treatments. The CTN steers tended to have heavier final BW (P = 0.09) and greater overall average daily gain (P = 0.08). The CTN steers had heavier hot carcass weight (P = 0.02) and greater fat thickness (P = 0.03) than CON steers, but marbling score and rib eye area were not different between treatments (P ≥ 0.64). Steers fed the CON diet tended to have a lower yield grade (P = 0.07), less kidney, pelvic and heart fat (P = 0.09), and decreased dressing percentage (P = 0.10) than CTN steers. Liver scores did not differ (P ≥ 0.17) between treatments. Fecal consistency scores were decreased for CTN steers on day 56 (P = 0.03) and fecal pH tended to be greater for the CTN steers on day 28 (P = 0.09) compared with CON steers, but neither differed during other periods (P ≥ 0.18). A treatment × day interaction (P = 0.04) was detected for plasma urea nitrogen (PUN) concentrations, where PUN concentrations differed between treatments only on days 28 and 56. On both days 28 and 56, CTN steers had lower PUN concentrations (P = 0.03, P = 0.002, respectively). No treatment × day interaction was detected for plasma glucose or lactate concentrations. A day effect was observed for both metabolites (P < 0.01). Results from this experiment suggest that cotton byproducts can be effectively used as a source of fiber, fat, and protein in feedlot rations without adverse effects on performance or carcass characteristics.